Involvement of cholecystokinin receptors in the control of striatal dopamine autoreceptors.
The interaction of locally perfused cholecystokinin-8 (sulphated) with systemically administered apomorphine was studied on the release of dopamine and its metabolites using microdialysis in the neostriatum of the halothane-anaesthetized male rat. Dialysate levels of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid were assayed by high performance liquid chromatography in combination with electrochemical detection. Perfusion with cholecystokinin-8 (100 microM but not 1 microM or 10 nM) increased the dialysate levels of dopamine without affecting those of DOPAC or HVA. At low concentrations (1 microM and 10 nM but not 1 nM), cholecystokinin-8 counteracted the inhibitory effect of apomorphine (0.05 mg/kg, s.c.) on dopamine release. This counteraction was antagonized by perfusion with the cholecystokinin-8 antagonist proglumide (3 microM). At this concentration, proglumide perfused alone was without effect on basal or apomorphine-reduced levels of dopamine. The results indicate a facilitatory effect of cholecystokinin-8 on dopamine release in rat neostriatum only at high concentrations. At lower concentrations, cholecystokinin-8 appears to modulate dopamine release by an inhibitory effect on dopamine autoreceptors possibly involving an intramembrane interaction between presynaptic cholecystokinin-8 receptors and dopamine autoreceptors.
Tanganelli
S
S
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Fuxe
K
K
von Euler
G
G
Agnati
L F
LF
Ferraro
L
L
Ungerstedt
U
U
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D011377:Proglumide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000502:physiology*; D011954:Receptors, Dopamine / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology
D011949:Receptors, Cholecystokinin; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D011377:Proglumide; D012844:Sincalide; D001058:Apomorphine; D004298:Dopamine; D006719:Homovanillic Acid